Procyanidin B2 protects against diet-induced obesity and non-alcoholic fatty liver disease via the modulation of the gut microbiota in rabbits

BACKGROUND Procyanidins have beneficial effects on metabolic syndrome and antimicrobial activity, but the mechanisms underlying these effects are unclear.AIM To investigate the effects of procyanidin B2(PB2) on non-alcoholic fatty liver disease and to explore the possible mechanism.METHODS Thirty male New Zealand white rabbits were randomized into three groups. All of them were fed either a high-fat-cholesterol diet(HCD) or chow diet. HCD-fed rabbits were treated with vehicle or PB2 daily for 12 wk. Body weight and food intake were evaluated once a week. Serum biomarkers, such as total cholesterols,triglycerides, and aspartate transaminase, were detected. All rabbits were sacrificed and histological parameters of liver were assessed by hematoxylin and eosin-stained sections. Moreover, several lipogenic genes and gut microbiota(by16 SrRNA sequencing) were investigated to explore the possible mechanism.RESULTS The HCD group had higher body weight, liver index, serum lipid profile, insulin resistance, serum glucose, and hepatic steatosis compared to the CHOW group.PB2 treatment prevented HCD-induced increases in body weight and hypertriglyceridemia in association with triglyceride accumulation in the liver.PB2 also ameliorated low-grade inflammation, which was reflected by serum lipopolysaccharides and improved insulin resistance. In rabbit liver, PB2 prevented the upregulation of steroid response element binding protein 1 c and fatty acid synthase and the downregulation of carnitine palmitoyltransferase,compared to the HCD group. Moreover, HCD led to a decrease of Bacteroidetes in gut microbiota. PB2 significantly improved the proportions of Bacteroidetes at the phylum level and Akkermansia at the genus level.CONCLUSION Our results indicate the possible mechanism of PB2 to improve HCD-induced features of metabolic syndrome and provide a new dietary supplement.